Forms of Albinism Presenting in Adulthood
Hermansky-Pudlak syndrome (HPS) is the primary form of albinism that characteristically presents with new manifestations in adulthood, specifically pulmonary fibrosis typically manifesting in the third decade of life. 1, 2
Hermansky-Pudlak Syndrome (HPS)
HPS is characterized by oculocutaneous albinism and bleeding diathesis present from birth, but pulmonary fibrosis often does not manifest until the third decade of life. 1, 2
Key Clinical Features:
- Oculocutaneous albinism (present from birth but patient may present for evaluation in adulthood) 1
- Bleeding diathesis due to platelet dysfunction 1
- Pulmonary fibrosis - the critical adult-onset manifestation, typically appearing in the third decade 1, 2
- Some patients develop granulomatous colitis or immunodeficiency 1
Genetic Basis:
- At least 10 genes implicated (AP3B1, HPS1, HPS3, HPS4, HPS5, HPS6, and less commonly AP3D1, BLOC1S3, BLOC1S6, DTNBP1) 1
- Autosomal recessive inheritance 1
- HPS1, HPS4, and AP3B1 genes are most strongly associated with pulmonary fibrosis 1
- Specific variants are more prevalent in Puerto Rican and Ashkenazi Jewish populations 1
Diagnostic Approach:
- Platelet electron microscopy should be performed in patients with clinical features suggestive of HPS 1
- Gene sequencing to confirm diagnosis 1
- HPS type 2 specifically may present with neutropenia and recurrent infections in addition to hypopigmentation and thrombocytopenia 1
Other Albinism Syndromes with Potential Adult Presentations
Chediak-Higashi Syndrome (CHS)
While CHS typically presents in childhood, patients who survive initial infections may develop an "accelerated phase" (hemophagocytic lymphohistiocytosis) that can occur in late adolescence or early adulthood. 1
Clinical features include:
- Partial oculocutaneous albinism (present from birth) 1
- Progressive neurological manifestations including cognitive impairment, photophobia, nystagmus, and cerebellar, spinal, and peripheral neuropathies 1
- Pyogenic bacterial infections affecting skin, respiratory tract, and other organs 1
- Giant azurophilic lysosomal granules in all granulated cells (pathognomonic finding) 1
Griscelli Syndrome Type 2 (GS2)
The accelerated phase of HLH in GS2 usually occurs in infancy or childhood but can be delayed until the second decade of life. 1
Clinical features include:
- Oculocutaneous hypopigmentation and silvery grey hair (present from birth) 1
- Recurrent pyogenic infections 1
- Neurological symptoms including seizures, ataxia, and oculomotor abnormalities 1
- Associated with RAB27A gene mutations 1
Important Clinical Distinctions
Non-Syndromic Oculocutaneous Albinism (OCA Types 1-4)
Classic OCA (types 1-4) does NOT present new manifestations in adulthood - all clinical features are present from birth, though pigment may accumulate over time in milder forms. 3, 4, 5
- OCA1A shows complete lack of melanin throughout life 3
- OCA1B, OCA2, OCA3, and OCA4 show some pigment accumulation over time but no new systemic manifestations 3
- All types feature congenital nystagmus, iris hypopigmentation, foveal hypoplasia, and reduced visual acuity present from birth 3
- Increased skin cancer risk requires lifelong surveillance but is not a "new presentation" 3
Dyskeratosis Congenita (DC)
While DC is a telomere syndrome with albinism-like features, pulmonary fibrosis may manifest in late adolescence or early adulthood, often after bone marrow transplantation. 1, 2
Critical Clinical Pitfall
The key distinction is between albinism syndromes where pigmentary changes are present from birth but systemic complications emerge in adulthood (HPS, CHS, GS2) versus classic OCA where all manifestations are congenital. 1, 3 When evaluating an adult with known childhood albinism who develops new symptoms, particularly pulmonary symptoms, bleeding diathesis, recurrent infections, or neurological deterioration, consider syndromic forms of albinism rather than isolated OCA. 1